1. Technical Field
The present invention relates to a remedy for chronic inflammation and a novel antibody to be used therein.
2. Background Art
The expression of tenascin-C is rarely observed in healthy cells, except for the immune system. Expression of tenascin-C is induced under pathological conditions such as inflammation and tumor growth.
As a method for detecting tenascin-C, some anti-tenascin-C antibodies have been known (for example, see JP-A Nos. 2004-217546 and 2002-234900). An arthritis diagnosis method using tenascin-C as a marker has been also known (for example, see JP-A-2004-138489).
A polypeptide which forms tenascin-C includes an epidermal growth factor-like domain, a fibronectin (FN) III-like domain and a fibrinogen-like domain. Among them, it has been known that the FN III-like domain includes a continuation between 8 basic types of repetitive sequences (1 to 8) and 9 types of repetitive sequences to be spliced (A1, A2, A3, A4, B, AD2, AD1, C and D), which are inserted between the fifth and the sixth sequences of the 8 basic types thereof. These repetitive sequence sites to be spliced are those easily cut by matrix metalloproteinases (MMP), and a peptide produced by a cut in tenascin-C by MMP are thought as having various functions.
On the other hand, it has been known that, in chronic inflammation, immune cells including monocytes such as macrophages and lymphocytes infiltrate from the blood vessels into the vascular endothelium and penetrate through the vascular basement membrane to gather at an inflammatory site. Such an immune cell infiltration at the inflammatory site is regulated by the interaction between immune cells, vascular endothelial cells and extracellular matrixes via adhesion molecules, integrins, on the immune cell membrane. It has been known that the integrins exist in two conformations, the active form and the inactive form and only the active form of integrins can adhere to extracellular matrixes.
A peptide derived from the A2 domain of the FNIII-like domain of tenascin-C (hereinafter may be referred to as “TNIIIA2”) has been known as a peptide causing the activation of the integrins (for example, see J. Biol. Chem., Vol. 282, pp. 34929-34937 (2007)).
However, no details have been given as to the roles of tenascin-C and the peptide derived therefrom in inflammatory sites, and in particular, there has been obtained no clear finding regarding their relationship with chronic inflammation. Further, there are cases that the effects of conventionally-known anti-tenascin-C antibodies against inflammation are inconsistent depending on the site.